Correlation of Antipsychotic and Prolactin Concentrations in Children and Adolescents Acutely Treated with Haloperidol, Clozapine, or Olanzapine

Abstract

Patients with a Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) diagnosis of schizophrenia or psychotic disorder not otherwise specified with onset of psychosis before the age of 13 participated in 6- to 8-week open or double-blind trials of haloperidol (n = 15, mean dose 15.4 +/- 8.1 mg/day [0.27 +/- 0.15 mg/kg/day]), clozapine (n = 30, mean dose 269.9 +/- 173.3 mg/day [4.4 +/- 2.6 mg/kg/day]), or olanzapine (n = 12, mean dose 17.5 +/- 2.8 mg/day [0.30 +/- 0.13 mg/kg/day]). Blood samples were obtained at 6 weeks for evaluation of haloperidol, reduced haloperidol, clozapine, desmethylclozapine, and olanzapine plasma concentrations and serum prolactin concentrations. No gender differences were noted for antipsychotic dose or concentration within each treatment group. Correlations between antipsychotic plasma concentration and serum prolactin concentration were significant only for the olanzapine treatment group (r = 0.80, p = 0.002). Separate correlations for gender were significant only for females receiving olanzapine (r = 0.91, p = 0.03); the patient with the highest serum prolactin experienced galactorrhea. Further studies evaluating the prolactin-elevating properties of antipsychotics are warranted in this population.

Prolactin Serum Concentrations During Aripiprazole Treatment in Youth

“…In response to antipsychotic medications such as olanzapine, risperidone and quetiapine, youth experience greater increases in serum PRL levels than do adults (Wudarsky et al 1999;Kinon et al 2003;Alfaro et al 2002;Becker and Epperson 2006;Migliardi et al 2009;Paing et al 2011;Cookson et al 2012). In contrast, after treatment with ARI, youth experience a far greater rate of subnormal PRL levels than do adults, as shown herein It is not clear what developmental processes account for the increased sensitivity of children to different antipsychotic agents influencing PRL release.…”

“…PRL serum levels are similar between male and female children, mildly higher in adolescents than in children, similar in adolescents as in adults, and generally higher in women of menstrual age (averaging 10-12 ng/mL) than in adult men (Friesen and Hwang 1973;Cook et al 1992;Siemens 2012). Adolescent females in most laboratory norms have mildly higher PRL levels than do adolescent males (Wiedemann et al 1993;Wudarsky et al 1999;Alfaro et al 2002). Variations in drug-induced PRL sensitivity by age…”

Antipsychotic Medication in Children and Adolescents: A Descriptive Review of the Effects on Prolactin Level and Associated Side Effects

“…These studies varied in terms of the duration of treatment, which ranged from 3.3 to 106 weeks. Six papers were based on the same clinical sample and study (Wudarsky et al 1999;Alfaro et al 2002;Aman et al 2002;Findling and McNamara 2004;Croonenberghs et al 2005;Reyes et al 2006). The samples included children with disruptive disorders, conduct disorder, oppositional defiant disorder, autism, schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorders not otherwise specified (NOS), Tourette's syndrome, bipolar affective disorder with psychotic features, depression with psychotic features, and children with normal and subnormal intelligence.…”

“…Seventeen studies had an open-label design, four studies had an observational design (Frazier et al 1999;Masi et al 2003;Stevens et al 2005;Staller 2006), and eight studies were double blind (Sallee et al 1996;Wudarsky et al 1999;Snyder et al 2002;404 ROKE ET AL. Alfaro et al 2002;Aman et al 2002;Sikich et al 2004;Hellings et al 2005;Luby et al 2006). Seven risperidone studies Findling and McNamara 2004;Croonenberghs et al 2005;Stevens et al 2005;Reyes et al 2006;Staller 2006;Anderson et al 2007) monitored prolactin for a period of 48-106 weeks.…”

Management of Adverse Effects of Second-generation Antipsychotics in Youth

“…Here, a few strategies could be considered: (1) reducing the dose of SGA, as there is some evidence to support that PRL elevation and PRL-related side effects are dose-dependent for risperidone and olanzapine [73,74]; (2) switching to a prolactin-sparing agent (clozapine, quetiapine, or aripiprazole); and (3) if SGA switch cannot be made, considering specialist consultation for further investigation and management. In the case of clinical concern and PRL-related side effects, consider specialist consultation for further investigation regarding other causes of hyperprolactinemia and/or amenorrhea.…”